Alzheimer's disease (AD) is the most common form of dementia. Most often, AD is diagnosed in people over 65 years of age, although the less prevalent early-onset AD can occur much earlier. AD worsens as it progresses and eventually leads to death. To date there is no cure for the disease. AD develops for an unknown and variable amount of time before becoming fully apparent, and it can progress undiagnosed for years.
AD is characterized by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus. Studies using MRI and PET have documented reductions in the size of specific brain regions in people with AD as they progressed from mild cognitive impairment to AD and in comparison with similar images from healthy older adults.
AD is usually diagnosed clinically from the patient history, collateral history from relatives, and clinical observations, based on the presence of characteristic neurological and neuropsychological features and the absence of alternative conditions. Advanced medical imaging with CT or MRI and SPECT or PET can be used to help exclude other cerebral pathology. Assessment of intellectual functioning including memory testing can further characterize the state of the disease. The diagnosis can be confirmed with very high accuracy post-mortem when brain material is available and can be examined histologically.
As can be derived from the above introductory statements taken from wikipedia (en.wikipedia.org), there is currently no reliable method of diagnosing AD in a living subject potentially suffering from the disease using a marker, i.e. an in vitro test, let alone of diagnosing an early stage of the disease using a marker.
As discussed in a recent review (Reddy and Beal; “Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease”; Trends in Molecular Medicine, Vol. 14 No. 2 (2008)), Aβ is known to localize to mitochondria and to cause mitochondrial damage. This intracellular Aβ and its toxic effect particularly on mitochondria are discussed as a rather early event during the progression of AD.
As noted above, there is no cure for AD; it appears only possible to alleviate some of the symptoms or to delay the onset of the disease. It is noteworthy in this respect that there are hints that anti-inflammatory agents and/or anti-oxidants can be beneficial for inhibiting or delaying the onset of AD since patients suffering from arthritis and treated with anti-inflammatory agents show a reduced rate of AD. This beneficial effect might particularly occur if AD patients are treated with anti-inflammatory agents or anti-oxidants at an early stage of the disease (see Marty “Anti-inflammatory drugs and Alzheimer's disease”; BMJ 2003; 327:353 and Breitner et al. “Extended results of the Alzheimer's disease anti-inflammatory prevention trial”; Alzheimers Dement. 2011; 7(4):402-411).
As is evident from the above, there is a strong need for markers indicating AD and methods of diagnosing AD, particularly in a living subject and at an early stage of AD. Furthermore, there is a strong need for developing effective medicaments against AD and for screening compounds for their activity against AD.